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301.
Qasem L Cardew A Wilson A Griffiths I Halsey LG Shepard EL Gleiss AC Wilson R 《PloS one》2012,7(2):e31187
Dynamic body acceleration (DBA) has been used as a proxy for energy expenditure in logger-equipped animals, with researchers summing the acceleration (overall dynamic body acceleration - ODBA) from the three orthogonal axes of devices. The vector of the dynamic body acceleration (VeDBA) may be a better proxy so this study compared ODBA and VeDBA as proxies for rate of oxygen consumption using humans and 6 other species. Twenty-one humans on a treadmill ran at different speeds while equipped with two loggers, one in a straight orientation and the other skewed, while rate of oxygen consumption () was recorded. Similar data were obtained from animals but using only one (straight) logger. In humans, both ODBA and VeDBA were good proxies for with all r2 values exceeding 0.88, although ODBA accounted for slightly but significantly more of the variation in than did VeDBA (P<0.03). There were no significant differences between ODBA and VeDBA in terms of the change in estimated by the acceleration data in a simulated situation of the logger being mounted straight but then becoming skewed (P = 0.744). In the animal study, ODBA and VeDBA were again good proxies for with all r2 values exceeding 0.70 although, again, ODBA accounted for slightly, but significantly, more of the variation in than did VeDBA (P<0.03). The simultaneous contraction of muscles, inserted variously for limb stability, may produce muscle oxygen use that at least partially equates with summing components to derive DBA. Thus, a vectorial summation to derive DBA cannot be assumed to be the more ‘correct’ calculation. However, although within the limitations of our simple study, ODBA appears a marginally better proxy for . In the unusual situation where researchers are unable to guarantee at least reasonably consistent device orientation, they should use VeDBA as a proxy for . 相似文献
302.
Cholesterol Treatment Trialists' 《PloS one》2012,7(1):e29849
Background
Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.Methods and Findings
Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).Conclusions
In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer). 相似文献303.
Thomas D Alcock Catherine L Thomas Seosamh
Lochlainn Paula Pongrac Michael Wilson Christopher Moore Guilhem Reyt Katarina Vogel-Miku Mitja Kelemen Rory Hayden Lolita Wilson Pauline Stephenson Lars
stergaard Judith A Irwin John P Hammond Graham J King David E Salt Neil S Graham Philip J White Martin R Broadley 《Plant physiology》2021,186(3):1616
Magnesium (Mg) and calcium (Ca) are essential mineral nutrients poorly supplied in many human food systems. In grazing livestock, Mg and Ca deficiencies are costly welfare issues. Here, we report a Brassica rapa loss-of-function schengen3 (sgn3) mutant, braA.sgn3.a-1, which accumulates twice as much Mg and a third more Ca in its leaves. We mapped braA.sgn3.a to a single recessive locus using a forward ionomic screen of chemically mutagenized lines with subsequent backcrossing and linked-read sequencing of second back-crossed, second filial generation (BC2F2) segregants. Confocal imaging revealed a disrupted root endodermal diffusion barrier, consistent with SGN3 encoding a receptor-like kinase required for normal formation of Casparian strips, as reported in thale cress (Arabidopsis thaliana). Analysis of the spatial distribution of elements showed elevated extracellular Mg concentrations in leaves of braA.sgn3.a-1, hypothesized to result from preferential export of excessive Mg from cells to ensure suitable cellular concentrations. This work confirms a conserved role of SGN3 in controlling nutrient homeostasis in B. rapa, and reveals mechanisms by which plants are able to deal with perturbed shoot element concentrations resulting from a “leaky” root endodermal barrier. Characterization of variation in leaf Mg and Ca accumulation across a mutagenized population of B. rapa shows promise for using such populations in breeding programs to increase edible concentrations of essential human and animal nutrients.“Leaky” root Casparian strips lead to accumulation of two-fold greater magnesium and ∼35% greater calcium concentrations in leaves of a Brassica rapa mutant. 相似文献
304.
We consider the Stag Hunt in terms of Maynard Smith’s famous Haystack model. In the Stag Hunt, contrary to the Prisoner’s
Dilemma, there is a cooperative equilibrium besides the equilibrium where every player defects. This implies that in the Haystack
model, where a population is partitioned into groups, groups playing the cooperative equilibrium tend to grow faster than
those at the non-cooperative equilibrium. We determine under what conditions this leads to the takeover of the population
by cooperators. Moreover, we compare our results to the case of an unstructured population and to the case of the Prisoner’s
Dilemma. Finally, we point to some implications our findings have for three distinct ideas: Ken Binmore’s group selection
argument in favor of the evolution of efficient social contracts, Sewall Wright’s Shifting Balance theory, and the equilibrium
selection problem of game theory. 相似文献
305.
Background
SXT is an integrating conjugative element (ICE) originally isolated from Vibrio cholerae, the bacterial pathogen that causes cholera. It houses multiple antibiotic and heavy metal resistance genes on its ca. 100 kb circular double stranded DNA (dsDNA) genome, and functions as an effective vehicle for the horizontal transfer of resistance genes within susceptible bacterial populations. Here, we characterize the activities of an alkaline exonuclease (S066, SXT-Exo) and single strand annealing protein (S065, SXT-Bet) encoded on the SXT genetic element, which share significant sequence homology with Exo and Bet from bacteriophage lambda, respectively.Results
SXT-Exo has the ability to degrade both linear dsDNA and single stranded DNA (ssDNA) molecules, but has no detectable endonuclease or nicking activities. Adopting a stable trimeric arrangement in solution, the exonuclease activities of SXT-Exo are optimal at pH 8.2 and essentially require Mn2+ or Mg2+ ions. Similar to lambda-Exo, SXT-Exo hydrolyzes dsDNA with 5'- to 3'-polarity in a highly processive manner, and digests DNA substrates with 5'-phosphorylated termini significantly more effectively than those lacking 5'-phosphate groups. Notably, the dsDNA exonuclease activities of both SXT-Exo and lambda-Exo are stimulated by the addition of lambda-Bet, SXT-Bet or a single strand DNA binding protein encoded on the SXT genetic element (S064, SXT-Ssb). When co-expressed in E. coli cells, SXT-Bet and SXT-Exo mediate homologous recombination between a PCR-generated dsDNA fragment and the chromosome, analogous to RecET and lambda-Bet/Exo.Conclusions
The activities of the SXT-Exo protein are consistent with it having the ability to resect the ends of linearized dsDNA molecules, forming partially ssDNA substrates for the partnering SXT-Bet single strand annealing protein. As such, SXT-Exo and SXT-Bet may function together to repair or process SXT genetic elements within infected V. cholerae cells, through facilitating homologous DNA recombination events. The results presented here significantly extend our general understanding of the properties and activities of alkaline exonuclease and single strand annealing proteins of viral/bacteriophage origin, and will assist the rational development of bacterial recombineering systems. 相似文献306.
307.
Mareli Claassens Cari van Schalkwyk Leonie den Haan Sian Floyd Rory Dunbar Paul van Helden Peter Godfrey-Faussett Helen Ayles Martien Borgdorff Donald Enarson Nulda Beyers 《PloS one》2013,8(4)
Background
In South Africa the estimated incidence of all forms of tuberculosis (TB) for 2008 was 960/100000. It was reported that all South Africans lived in districts with Directly Observed Therapy, Short-course. However, the 2011 WHO report indicated South Africa as the only country in the world where the TB incidence is still rising.Aims
To report the results of a TB prevalence survey and to determine the speed of TB case detection in the study communities.Methods
In 2005 a TB prevalence survey was done to inform the sample size calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It was a cluster survey with clustering by enumeration area; all households were visited within enumeration areas and informed consent obtained from eligible adults. A questionnaire was completed and a sputum sample collected from each adult. Samples were inoculated on both liquid mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen media. A follow-up HIV prevalence survey was done in 2007.Results
In Community A, the adjusted prevalence of culture positive TB was 32/1000 (95%CI 25–41/1000) and of smear positive TB 8/1000 (95%CI 5–13/1000). In Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI 17–32/1000) and of smear positive TB 9/1000 (95%CI 6–15/1000). In Community A the patient diagnostic rate was 0.38/person-year while in community B it was 0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19–30%).Discussion
In both communities a higher TB prevalence than national estimates and a low patient diagnostic rate was calculated, suggesting that cases are not detected at a sufficient rate to interrupt transmission. These findings may contribute to the rising TB incidence in South Africa. The TB epidemic should therefore be addressed rapidly and effectively, especially in the presence of the concurrently high HIV prevalence. 相似文献308.
Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related) structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life. 相似文献
309.
310.
Kithsiri Herath Gowi Bhat Paul L. Miller Sheng-Ping Wang Alison Kulick Genevieve Andrews-Kelly Christopher Johnson Rory J. Rohm Michael E. Lassman Stephen F. Previs Douglas G. Johns Brian K. Hubbard Thomas P. Roddy 《Analytical biochemistry》2011,415(2):197
Protein synthesis can be estimated by measuring the incorporation of a labeled amino acid into a proteolytic peptide. Although prelabeled amino acids are typically administered, recent studies have tested 2H2O; the assumption is that there is rapid equilibration of 2H (in body water) with the carbon-bound hydrogens of amino acids before those amino acids are incorporated into a protein(s). We have determined the temporal changes in 2H labeling of body water and amino acids which should build confidence in 2H2O-based studies of protein synthesis when one aims to measure the 2H labeling of proteolytic peptides. 相似文献